JP2020190749A - Methods, systems and apparatus for reducing frequency and/or severity of photophobic responses or for modulating circadian cycles - Google Patents

Abstract

To provide an optical filter that may reduce the frequency and/or severity of photophobic responses or modulate circadian cycles by controlling exposure of cells in a human eye to light in certain wavelengths, such as 480 nm and 590 nm, and a visual spectral response of the human eye, where the optical filter may disrupt isomerization of melanopsin in the human eye reducing the availability of the active isoform, whereas attenuation of light weighted across the action potential spectrum of the active isoform attenuates the phototransduction cascade leading to photophobic responses.SOLUTION: An optical filter may be configured to transmit less than a first amount of light in certain wavelengths, and to transmit more than a second amount of light weighted across the visual spectral response.SELECTED DRAWING: Figure 26

Description

Cross-reference of related applications
[0001] The present application was filed on July 22, 2014, and the title of the invention is "METHODS, SYSTEMS, AND APPARATUS FOR REDUCING THE FREQUENCY AND / OR SEVERITY OF PHOTOPHOBIC RESPONSESOR CRUNS OR And / or methods, systems, and devices that reduce the degree or adjust the circadian rhythm) ”claim priority and interests under US Patent Application No. 14 / 338,182. All of the aforementioned applications are incorporated herein by reference in their entirety.

[0002] Photophobia or photosensitivity represents an adverse response to light that characterizes some neurological symptoms. The present invention relates to controlling the effect of light on the subject. More specifically, the present invention relates to methods, systems, and devices that reduce the frequency and / or extent of photophobic reactions or regulate circadian cycles.

[0003] The retina of the eye contains various photoreceptor cells. These photoreceptor cells include rods (involved in black-and-white and low-light vision), cones (involved in daytime vision and color vision), and melanopsin ganglion cells.

[0004] Melanopsin ganglion cells are photosensitive. This photosensitivity can transmit pain through the pain transmission pathways of the brain. These transmission pathways are incorporated herein by reference in their entirety, such as Noseda et al., A Neuromechanism for Exercise of Headache by Light (Neural Mechanisms in Light-induced Headache Exacerbation), Nat Neurosci. February 2010; 13 (2): 239-45 PMID20062053. It has long been demonstrated that accommodating ambient light by coloring eyeglasses can be effective in the treatment of photosensitive neurological symptoms, including migraines and benign idiopathic blepharospasm. A description of these beneficial effects, both incorporated herein by reference, by Good et al., The Use of Tinted Glasses in Childhood Glasses, Headache. September 1991; 31 (8): 533-6PMID1960058 and Blackburn et al., FL-41 Tint Improves Blink Frequency Light Sensitivity and Functional Limity Blepharospasm Blepharospasm Blepharospasm Blink frequency Improves photosensitivity and functional limitation), Ophthalmology. May 2009; 116 (5): 997-1001 PMID 19410598. Melanopsin ganglion cells are also connected to the suprachiasmatic nucleus in addition to the pain transmission pathway, and melanopsin ganglion cells are involved in the synchronization of circadian rhythms in the suprachiasmatic nucleus. These bindings are incorporated herein by reference in their entirety, Hannibal J. et al. , Roles of PACAP-contining retinal ganglion cells in circadian timing (role of PACAP-containing retinal ganglion cells in circadian timing), Int Rev Cytor. 2006; 251: 1-39. Review. It is described in more detail by PubMed PMID: 16939776.

[0005] All animals have an intrinsic "clock" that synchronizes them to the Earth's 24-hour light / dark cycle. This watch establishes an internal rhythm of about ("circa") and one day ("dian"). This phenomenon is incorporated herein by reference in its entirety, Czeisler CA, Gooley JJ. , Sleep and circadian rhythms in humans (human sleep and circadian rhythm), Cold Spring Herb Symp Quant Biol. 2007; 72: 579-97. Review. It is described by PubMed PMID: 18419318. However, the body clock must be reset daily to keep it optimally synchronized with the dark / light cycle. Czeisler CA, The effect of light on the human circadian pacemaker (the effect of light on a person's circadian pacemaker), Ciba Found Symp., Both of which are incorporated herein by reference in their entirety. 1995; 183: 254-90; discussion 290-302. Review. PubMed PMID: 7656689 and Duffy JF, Wright KP Jr. , Entry of the human circadian system by light (synchronization of human circadian system by light), J Biol Rhythms. August 2005; 20 (4): 326-38. Review. According to PubMed PMID: 160777152, when melanopsin ganglion cells absorb light in the surrounding environment and transmit a signal to the suprachiasmatic nucleus, which is the part of the brain that functions as the "main clock" of the body. , This tuning occurs.

[0006] Rhodopsin is a photosensitive molecule in the rod and cone of the eye. Rhodopsin contains two metastable isomers, including an active state and an inactive state. Rhodopsin isomerizes to an inert isoform when exposed to light. The inactive isoform of rhodopsin can be restored during the retinoid cycle. During the retinoid cycle, rhodopsin leaves the photoreceptors and enters the retinal pigment epithelium. After being restored to the active isoform, rhodopsin returns to the photoreceptor. Melanopsin ganglion cell melanopsin, which is incorporated herein by reference in its entirety, is from Mure LS, Cornut PL, Rieux C, Drouyer E, Denis P, Gronfier C, Cooper HM, Melanopsin retina display: af. in the human retina (melanopsin bistable: fly eye technology in the human retina), PLoS One. June 24, 2009; 4 (6): e5991. It is believed to go through a process similar to the process described in PubMed PMID: 19551136.

[0007] Therefore, it is desired to control the effect of light on the subject. More specifically, it is desired to provide methods, systems, and devices that reduce the frequency and / or extent of photophobic reactions. It is also desired to provide methods, systems, and devices for adjusting the circadian rhythm.

[0008] Melanopsin ganglion cells are sensitive to wavelengths of light near 480 nm and are involved in pain transmission pathways in humans, thus controlling the painful effects caused by certain types of light. desirable. For example, stimulation of melanopsin ganglion cells can affect the frequency and / or degree of photophobic response, thus reducing direct photostimulation of these cells in some situations, or in other situations, It may be beneficial to reduce exposure to light that is not directly related to the stimulation of these cells. These photophobic reactions include migraine headaches, photosensitivity associated with shaking or traumatic brain injury, photosensitive epilepsy, and photosensitive epilepsy associated with benign idiopathic blepharospasm. Melanopsin ganglion cells are also involved in the circadian cycle. Thus, methods, systems, and systems that reduce the frequency and / or degree of photophobic response and / or regulate the circadian cycle by controlling exposure to light of melanopsin ganglion cells or other parts of the eye. Equipment is provided.

[0009] A device of one embodiment that reduces the frequency and / or degree of photophobic reaction or regulates the circadian cycle will be described. The device transmits light less than the weighted first light intensity over the absorption spectrum of the melanopsin bistable isoform and more light than the weighted second light intensity over the visual spectral response. Includes an optical filter configured in. By way of example, the optical spectrum related to the absorption spectrum of the active isoform of melanopsin has a wavelength of around 480 nm, and the optical spectrum related to the absorption spectrum of the inactive isoform of melanopsin has a wavelength of around 590 nm.

[0010] In some embodiments, the first amount of light is about 50% of the light weighted over the absorption spectrum of one or both of the melanopsin bistable isoforms, and the second amount of light is the visual spectral response. More than about 75% of the light weighted over. In other embodiments, the first amount of light is about 25% of the light weighted over the absorption spectrum of one or both of the bistable isoforms of melanopsin, and the second amount of light is weighted over the visual spectral response. It is about 60% or more of light. In another embodiment, the first amount of light is approximately the entire weighted light over the absorption spectrum of one or both of the melanopsin bistable isoforms. In another different embodiment, the second amount of light is weighted outside the absorption spectrum of one or both of the melanopsin bistable isoforms and / or across the visual response spectrum, one or one of the melanopsin bistable isoforms. Approximately the entire light weighted over spectra outside both absorption spectra. In yet another embodiment, the ratio of the attenuation of the first light intensity weighted over one or both absorption spectra of the melanopsin bistable isoform to the attenuation of the second light intensity weighted over the visual spectral response is 1. Exceeds.

[0011] In some embodiments, the first amount of light is substantially all of the light below the wavelength of the longpass filter within the active potential spectrum of the melanopsin ganglion cells, and the second amount of light is of the longpass filter. All light over the visual spectral response, including wavelengths above wavelength. In another embodiment, the first amount of light is substantially all of the light above the shortpass filter wavelength near 590 nm and the second amount of light spans the visual spectral response including wavelengths below the shortpass filter wavelength. Can be virtually all of.

[0012] In some embodiments, the second light intensity comprises a wavelength less than the maximum relative response of the action potential spectrum of the melanopsin ganglion cells and / or a third light intensity comprising a wavelength greater than about 590 nm. In other embodiments, the second amount of light comprises a third amount of light that includes a wavelength greater than the maximum relative response of one or both absorption spectra of the melanopsin bistable isoform. In another embodiment, the second light intensity is a third light intensity that contains a wavelength less than the maximum relative response of one or both absorption spectra of melanopsin and one or both of the melanopsin bistable isoforms. Includes a fourth amount of light that is greater than the maximum relative response of the absorption spectrum of.

[0013] In some embodiments, the first amount of light is the cells in the eye (ie, across the absorption spectrum of one or both of the bistable isoforms of melanopsin) -the subject's retinal ganglion cells or others. The amount of light received by the cells (D _rec ), the second amount of light is the amount of light received over the visual response spectrum (D _vis ), and the ratio including the first amount of light and the second amount of light is the performance index (D _rec ). It is defined as FOM (figure of merit), and the performance index is calculated by the following equation.

In the equation, D _rec (T = 1) is the first amount of light when there is no optical filter, and D _vis (T = 1) is the second amount of light when there is no optical filter. In some embodiments, the figure of merit of the optical filter is about 1, greater than about 1, greater than about 1.3, greater than about 1.5, greater than about 1.8, greater than about 2.75. It can contain values greater than about 3 and greater than about 3.3. In other embodiments, other figure of merit may be used.

[0015] In some embodiments, the first light intensity defines a spectral width that is median at the median of the absorption spectrum of one or both of the melanopsin bistable isoforms. In another embodiment, the first light intensity and the second light intensity are determined based on the characteristics of the ambient light. In another different embodiment, the first and second light intensity can be selectively adjusted by transition, -light tautomerization, or electrocoloring dyes, dyes or coatings.

[0016] In some embodiments, the optical filter comprises at least one layer configured to minimize or reduce the effect of the angle of incidence of the received light. In another embodiment, the optical filter further comprises a substrate comprising coloration by impregnation or coating.

[0017] A system of one embodiment that reduces the frequency and / or degree of photophobic reaction or regulates the circadian cycle will be described. The system includes a substrate, a first layer disposed on the substrate, and a second layer disposed adjacent to the first layer. The first layer contains a high refractive index material. The second layer contains a low index of refraction material.

[0018] In another embodiment, the system may include additional layers and / or material types, the materials working together to be less than the first light intensity weighted over the action potential spectrum of melanopsin ganglion cells. Light is transmitted, and light exceeding the weighted second amount of light is transmitted over the visual spectral response. In some embodiments, increasing the number of layers in the optical filter increases the transmission of light outside the action potential spectrum.

[0019] A method of an embodiment of manufacturing an optical filter that reduces the frequency and / or degree of photophobic reaction will be described. The method comprises the step of determining an appropriate optical spectrum. The amount of first light received by one or both of the melanopsin bistable isoforms in the subject is determined. A second amount of light related to the visual response spectrum is determined. An optical filter is manufactured using the first amount of light and the second amount of light.

[0020] In some embodiments, the action potential spectrum of human melanopsin ganglion cells is determined. In another embodiment, the optical filter is configured to attenuate the first amount of light based on human melanopsin ganglion cells. In another different embodiment, the optical filter is manufactured based on visual response spectral characteristics.

[0021] In some embodiments, the optical filter is a notch filter. In another embodiment, the notch filter is configured to block light emitted at a non-vertical angle of incidence. In another different embodiment, the notch filter includes a filter optimized for multiple tilted angles of incidence. In yet another embodiment, the notch filter is designed with a slight redshift. In yet another embodiment, the notch filter comprises a filter notch that attenuates light over a certain spectral width.

[0022] In some embodiments, the manufacture of optical filters uses multilayer dielectrics, nanoparticle embedding coatings, color filters, coloring, resonant waveguide mode filters, lugate filters, and any combination thereof. Including that. In another embodiment, the nanoparticle-embedded coating is a core-shell particle having metal nanoparticles, dielectric nanoparticles, semiconductor nanoparticles, quantum dots, magnetic nanoparticles, or a core material in the core and a shell material that acts as a shell. Includes at least one. In another different embodiment, the metal nanoparticles contain at least one of Al, Ag, Au, Cu, Ni, Pt, or other metal nanoparticles, and the dielectric nanoparticles are TiO ₂ , Ta. ₂ O ₅ or at least one of the other dielectric nanoparticles. In yet another embodiment, the semiconductor nanoparticles or quantum dots include at least one of Si, GaAs, GaN, CdSe, CdS, or other semiconductor nanoparticles. In yet another embodiment, the shape of the embedded nanoparticles in the nanoparticle embedding coating is spherical, elliptical, or another shape. In some embodiments, the decay spectrum of the embedded nanoparticles is determined using Mie scattering theory.

[0023] A method of one embodiment of reducing the frequency and / or degree of photophobic reaction or adjusting the circadian cycle will be described. The method includes the step of receiving some amount of light. Light less than the first weighted amount of light is transmitted over the absorption spectrum of one or both of the melanopsin bistable isoforms. Light that exceeds the weighted second amount of light is transmitted over the visual spectrum response. Light attenuation weighted over the absorption spectrum of one or both of the melanopsin bistable isoforms interferes with the isomerization of one or both of the melanopsin bistable isoforms.

[0024] The drawings form part of the specification and include exemplary embodiments of the invention that can be embodied in various forms. In some examples, it is understood that various aspects of the invention may be exaggerated or expanded to facilitate understanding of the invention.

[0025] FIG. 5 shows an exemplary measurement action potential spectrum of melanopsin cells normalized to a unit quantity and a Gaussian fitting to a measurement data point. [0026] FIG. 6 shows a measurement transmission spectrum of an exemplary "FL-41 35" filter over the "effective action potential spectrum" of melanopsin. [0027] FIG. 6 shows a measurement transmission spectrum of an exemplary "FL-41 35" filter over the visible light spectrum. [0028] FIG. 6 shows a measurement transmission spectrum of an exemplary "FL-415" filter over the "effective action potential spectrum" of melanopsin. [0029] FIG. 6 shows a measurement transmission spectrum of an exemplary "FL-41 55" filter over the visible light spectrum. [0030] It is a figure of an exemplary filter using a multilayer dielectric thin film having a different refractive index. [0031] FIG. 5 is an exemplary filter diagram using a nanoparticle embedded coating designed to scatter light in the turquoise region of the visible light spectrum. [0032] FIG. 6 illustrates an exemplary method of designing an optical filter that interferes with light absorption by melanopsin cells. [0033] FIG. 6 shows a measured transmission spectrum of a filter of one embodiment over the "effective action potential spectrum" of melanopsin. [0034] It is a figure which shows the measurement transmission spectrum of the filter of the embodiment shown in FIG. 9 over the visible light spectrum. [0035] It is a figure which shows the measured transmission spectrum of the filter of another embodiment over the "effective action potential spectrum" of melanopsin. [0036] It is a figure which shows the measured transmission spectrum of the filter of another embodiment over the "effective action potential spectrum" of melanopsin. [0037] FIG. 6 shows the measured transmission spectra of filters of different different embodiments across the "effective action potential spectrum" of melanopsin. [0038] It is a figure which shows the measurement transmission spectrum of the filter of the embodiment shown in FIG. 13 over the visible light spectrum. [0039] FIG. 6 shows a measured transmission spectrum of a filter of yet another embodiment, with the center of the filter located at 485 nm with respect to vertically incident light, over the "effective action potential spectrum" of melanopsin. [0040] FIG. 6 shows a measurement transmission spectrum of the embodiment shown in FIG. 15 with an incident angle of 15 degrees over the "effective action potential spectrum" of melanopsin. [0041] It is a figure which shows the measured transmission spectrum of the filter of yet another embodiment except for the low refractive index MgF ₂ layer over the "effective action potential spectrum" of melanopsin. [0042] FIG. 18A is a diagram showing a measurement transmission spectrum of a filter of one embodiment centered on about 480 nm. FIG. 18B is a diagram showing a measurement transmission spectrum of the filter of one embodiment centered on about 620 nm. [0043] It is a figure which shows the measurement transmission spectrum of the filter of a plurality of embodiments centering on about 480 nm of various degree of coloring. [0044] FIG. 6 shows a rear reflection spectrum of the filter of the embodiment shown in FIG. [0045] FIG. 6 illustrates an exemplary embodiment of a method of manufacturing an optical filter. [0046] FIG. 6 illustrates an exemplary embodiment of a method of reducing the frequency and / or degree of photophobic reaction or adjusting the circadian cycle. [0047] FIG. 6 shows a composite filter of one embodiment configured to preferentially attenuate two wavelength ranges. [0048] It is a figure which shows one Embodiment of the method of manufacturing a composite optical filter. [0049] FIG. 6 illustrates an embodiment of a method of reducing the frequency and / or degree of photophobic reaction or adjusting the circadian cycle using a composite filter. [0050] FIG. 26A is a diagram showing a transmission spectrum of a gray-colored lens coating centered on 480 nm. FIG. 26B is a diagram showing a transmission spectrum of a gray-colored lens coating centered on 620 nm. [0051] FIG. 5 is a diagram schematically showing the cyclic isomerization of a bistable dye. [0052] It is a figure which shows the response spectrum of active melanopsin and inactive melanopsin in the eye. [0053] FIG. 6 illustrates an embodiment of a method of interfering with the isomerization of one or both of the bistable isoforms of melanopsin.

A detailed description of embodiments of the present invention is provided herein. However, it is understood that the present invention can be embodied in various forms. Accordingly, the specific details disclosed herein are not construed as limiting, but rather teach those skilled in the art how to utilize the invention in virtually any system, structure, or method. Interpreted as a representative basis for.

[0055] The present invention relates to controlling the effect of light on a subject. Some applications of the present invention relate to methods, systems, and devices that reduce the frequency and / or extent of photophobic reactions or adjust the circadian cycle.

[0056] Different people experience photophobic reactions in different ways. The wavelengths that cause adverse reactions to light and the associated transmission pathways can vary from patient to patient. However, there are some common wavelengths that are more commonly associated with photophobic reactions than others. For example, melanopsin ganglion cells in the eye are sensitive to light at a wavelength of about 480 nm. For some people, this may be related to the neurological symptoms of their photosensitivity. Controlling exposure to light near a wavelength of 480 nm is beneficial to these individuals and may reduce or prevent the neurological symptoms of their photosensitive epilepsy. Alternatively, or in addition, adjusting its exposure to the same light can also help control a person's circadian rhythm. Adjusting eye exposure to light at wavelengths near 620 nm or other wavelengths in the same person or others reduces or prevents neurological symptoms of photosensitive epilepsy, or reduces a person's circadian rhythm. It can also be an advantage in controlling. The following examples refer to the attenuation of light containing wavelengths near 480 nm and the exposure of melanopsin ganglion cells to the same light near 480 nm, although similar filters and methods can be used at other wavelengths in the eye. It will be appreciated that it can be used to attenuate the light received by other cells. For example, similar filters and methods can be used to attenuate light at 620 nm or about 620 nm. In other examples, similar filters and methods can be used to attenuate light at 590 nm or about 590 nm.

[0057] Since melanopsin ganglion cells are said to be responsible for the development of photophobia and migraines in many photophobic patients, they shield at least part of the visible spectrum that activates these cells. Is desirable. Photophobia is associated with the neurological symptoms of photosensitive epilepsy, including migraine headaches, benign idiopathic blepharospasm, and traumatic brain injury (TBI). FIG. 1 shows measurement action potential spectra of melanopsin cells normalized to exemplary unit quantities and Gaussian fittings to measurement data points. This Gaussian fitting can be used in the filter design of at least one embodiment, but since more accurate measurements of the active (activation) potential spectrum may be available, this Gaussian fitting is a spectrum for optimal filters. It should not be interpreted as a standard of. This accurate measurement may lead to another filter design or method according to or through a process described herein. It is intended to optimize the methods, systems, and equipment described herein based on more accurate measurements of action potential spectra.

[0058] In some embodiments, light can be occluded (ie, attenuated) over a specific wavelength range suitable for preventing photophobia, while minimizing visible spectrum distortion. In other embodiments, the methods, systems, and devices described in this application can also be used to manipulate the circadian system of the body.

[0059] An embodiment of an optical filter that shields a specific part of the optical spectrum suspected of developing and / or exacerbating these photophobic reactions will be described. These filters include eyewear (such as eyeglasses, goggles, clip-ons, or other eyewear), lenses (including contact lenses), computer screens, windows, car windshields, lighting substrates, and bulbs (incandescent bulbs,). It can be applied to fluorescent lamps, CFLs, LEDs, gas vapors, etc.), or any other optical element. These optical filters are crown glass (including BK7), flint glass (including BaF _8), SiO _2, plastic (polycarbonate, CR-39, and the like Trivex), another base material, and, combinations thereof Can be applied.

[0060] Although most of the description focuses on the prevention of photophobia, the systems, methods, and devices described herein are also applicable to regulating circadian rhythms. For example, these filters are used to manipulate the circadian system of the body by entrepreneurs, athletes, others, or anyone who wishes to manipulate the genital system of the body, traveling between different time zones. obtain. In one example, the subject wears at least one filter as described herein, which helps adapt the subject to the light / dark cycle of where the subject moves. In another example, at least one of the filters described herein can also be used to limit the excitation of melanopsin ganglion cells in patients with sleep disorders. In this application, the subject wears these filters to limit the subject's exposure to artificial light at night, and the subject's body clock determines that it is time to wake up. To prevent that. In addition, the subject may adjust the subject's light / dark cycle by increasing exposure to light before sunrise.

[0061] Furthermore, it has recently been clinically demonstrated that wavelengths near 620 nm also contribute to the photophobic effect in certain individuals. The exact transmission pathways for neurological effects are not well understood so far, but similarly, the benefits can be achieved by preferentially attenuating light containing wavelengths near 620 nm.

[0062] Melanopsin contains bistable isoforms, each showing a unique absorption spectrum. The isoforms can be active and inactive isoforms. The active isoform can be physiologically active. The Inactive Isoform can be physiologically inactive. Absorption of light based on the absorption spectrum of each isoform can result in melanopsin isomerization. Benefits can be achieved by interfering with, limiting, or preventing melanopsin isomerization by attenuating light at 590 nm or about 590 nm.

[0063] FL-41 lens coloring may be applied to migraine patients. FL-41 coloring shields a wide wavelength range (by absorption). These wavelengths include wavelengths related to melanopsin absorption. The FL-41 dye can penetrate certain types of plastic spectacle lenses. The amount of dye penetrated, as a whole, determines the degree of light intensity that is blocked. "FL-41 35" coloring is effective for many patients in an indoor environment. However, for example, if the light source is increased in intensity by moving to an outdoor environment, "FL-41 35" may not be as effective as it is.

[0064] FIG. 2 shows the measured transmission spectrum of “FL-41 35”. FIG. 2 further shows the effect of the “FL-41 35” filter on the action potential spectrum of melanopsin, which is called the “effective action potential spectrum”. "FL-41 35" coloring blocks or attenuates approximately 55% of the light absorbed by melanopsin ganglion cells in the absence of that coloring. In addition, as shown in FIG. 3, FL-41 coloring masks most of the melanopsin-independent visible spectrum and attenuates it by about 47% over the visual response spectrum. Further shielding the visible response spectrum can be detrimental. For example, shielding the visible response spectrum can adversely affect normal vision. In another example, shielding the visible response spectrum can produce an undesired color scheme that can be distracting or less desirable to the wearer.

[0065] In bright light conditions, such as in an outdoor environment, coloring with a higher level of spectral attenuation, such as "FL-41 55", may be used. The transmission spectrum of this filter and the effect of the filter on the action potential spectrum are shown in FIGS. 4 (over the "effective action potential spectrum" of melanopsin) and FIG. 5 (over the visible light spectrum). This filter attenuates about 89% of the light absorbed by melanopsin cells without the filter, but also attenuates about 81% of the visual response spectrum. This further spectral attenuation can further impair vision at low light levels or in other situations.

[0066] Overall, the general drawbacks of FL-41 are its rosy appearance, color vision distortion, and limited scope (ie, it can only be applied to certain plastics, glass lenses, computer screens, etc. May not apply to windows, car windshields, lighting substrates, light bulbs, or other optics) and poor quality control over the coloring process (partially due to variations in the hard coating layer that can be colored) ) And include. Although FL-41 may be effective in certain applications, it is not designed to down-regulate the stimulation of melanopsin ganglion cells and their connection to the pain center of the brain. For these reasons, it may be desirable to develop filters of other embodiments.

[0067] An example of a more desirable optical filter for the treatment of photosensitivity may include a long pass filter. To regulate the exposure of melanopsin ganglion cells to a wavelength of about 480 nm, longpass filters can transmit more wavelengths longer than about 500 nm or 520 nm, while attenuating light at wavelengths shorter than about 500 nm or 520 nm. Similarly, to regulate the exposure of cells in the human eye to wavelengths of about 620 nm, shortpass filters can transmit more wavelengths shorter than 600 nm or about 580 nm, while light with wavelengths longer than about 600 nm or about 580 nm. Attenuates.

[0068] Another example of a more desirable optical filter is to block only the spectrum of light absorbed by melanopsin or other specific wavelengths, while allowing the rest of the optical spectrum to pass through the entire spectrum of the filter. It may include a filter, sometimes called a band elimination filter or a negative filter, where the transmission response takes the form of a notch. In the case of melanopsin, the central position of the notch can be close to the maximum absorption wavelength (about 480 nm) of the melanopsin transmission pathway, but other positions can be effective. The spectral width of the notch can roughly match the width of the action potential spectrum, which is about 50-60 nm, but other widths are possible.

[0069] Coloring containing dye mixtures, multilayer dielectrics (an example shown in FIG. 6), nanoparticle embedded coatings (an example shown in FIG. 7), other filter technologies such as resonant waveguide filters, or combinations thereof. Optical filter technology can be used to form filters in accordance with the present disclosure. The nanoparticle coatings that can be used in optical filters according to the present disclosure are metal nanoparticles (eg, Al, Ag, Au, Cu, Ni, Pt), dielectric nanoparticles (eg, TiO ₂ , Ta ₂ O _5). ), Semiconductor nanoparticles or quantum dots (eg Si, GaAs, GaN, CdSe, CdS, etc.), magnetic nanoparticles, core-shell particles consisting of one material in the core and another material that acts as a shell, other nano It may include particles, or a combination thereof. The shape of these particles can be spherical, ellipsoidal, other shapes, or a combination thereof. The base material may include polymers, sol-gels, other base materials, or a combination thereof. The decay spectra of these nanoparticles can be calculated using Mie scattering theory or its derivatives.

[0070] The multilayer filter 600 of one embodiment shown in FIG. 6 includes a base material 602, a first layer 604, and a second layer 606. As shown in the figure, the first layer 604 may contain a high refractive index material and the second layer 606 may contain a low refractive index material. In another embodiment, the first layer 604 may contain a low index of refraction material and the second layer may contain a high index of refraction material. In addition, the first layer 604 is shown adjacent to the substrate 602. In other embodiments, the first layer 604 may include another layer (eg, a second layer 606 and / or another layer) between the substrate 602 and the first layer 604. Another layer is also shown (but unsigned). As the base material 602, any base material described in the present specification can be used. For example, the substrate 602 may include a colored layer (not shown) on the same side and / or opposite side as the first layer 604 and the second layer 606 (ie, anterior and / or posterior to the substrate). .. In another example, the substrate 602 itself can penetrate the color. An exemplary coloring technique and amount of coloring will be described below. Multilayer filters of other embodiments will be further described herein.

[0071] The filter 700 shown in FIG. 7 includes a base material 702, a base material layer 704, and a plurality of nanoparticles 706. The base metal layer 704 is shown adjacent to the substrate 702. In other embodiments, the base metal layer 704 may include another layer (eg, a second layer 606 and / or another layer shown in FIG. 6) between the base material layer 702 and the base metal layer 704. However, the nanoparticles 706 are shown as spherical and of uniform size, but as mentioned above, further other shapes and dimensions are conceivable. As with the multilayer filter of FIG. 6, various substrates, colors, other features, or combinations thereof can be used with the nanoparticle filter 700. Nanoparticle filters of other embodiments will be described herein.

[0072] Other types of filters that may be used may include color filters (organic dyes and semiconductors), resonant waveguide mode filters, lugate filters, or a combination thereof. Lugate filters utilize a sinusoidal change in index of refraction over their thickness. True sinusoidal functions may not be available and are often approximated by a stepped index approximation using a mixture of two or more materials.

[0073] In addition to these various filter types, further considerations may take into account the effect of the designed filter on the visual response spectrum, which is determined by the photoreaction of the rod and cone. One of the considerations may include minimizing spectral distortion. Considering the blueshift of the filter response that occurs to off-axis irradiation, the notch center is designed to be slightly redshifted from about 480 nm, for example towards melanopsin ganglion cells. Consider adding additional or other constraints to the filter design, including optimization methods such as taking into account angular sensitivity, which can be compensated for using multilayer dielectrics when attenuating light near 480 nm. Can be done. The degree of redshift or blueshift can vary depending on the wavelength being attenuated. Optimization can further include widening the spectral width of the filter to compensate for the non-vertical angle of incidence and / or compensating for the angle of incidence by using an additional filter layer. The possibility of posterior reflexes can be a consideration. One or more of these considerations can be addressed by combining some form of colored filter.

[0074] An embodiment of a method of producing an optical filter that interferes with light absorption by melanopsin cells will be described herein. The amount of light D received by melanopsin cells can be expressed by the following equation.
D _melan = ∫L (λ) T (λ) M (λ) dλ (1)
In the equation, L is the light spectrum (in terms of intensity, output, photons / sec, etc.), T is the spectral transmittance of the filter located between the light source and the eye, and M is the current spectrum from FIG. It is a normalized activity potential response spectrum of melanopsin estimated to be a Gaussian function having a full width at half maximum of 52 nm centered on 480 nm. For generalization, we assume L = 1 so that the description is not limited to any particular light source, but the analysis can be performed on any light source with a known spectrum.

A similar amount of light can be calculated in relation to the visual response spectrum.
D _vis = ∫L (λ) T (λ) V (λ) dλ (2)
In the equation, V represents a normalized visual response spectrum.

[0076] The effect of an optical filter such as FL-41 coloring is explained by taking the ratio of the amount of light calculated using the filter to the amount of light when the filter is not used, for example, as in the following equation. This is to reduce the amount of light.

[0077] The "attenuation" of the amount of light can be expressed, for example, by the following equation.

A figure of merit (FOM) can also be defined that compares the occlusion of the melanopsin response with the occlusion of the visual response spectrum.
This equation represents the ratio of the attenuation of light over the melanopsin spectrum to the attenuation of light over the visible spectrum, in which the FOM value> 1 may be desirable. In the case of FL-41 coloring, the FOM is about 1.

FIG. 8 shows an embodiment of method 800 for designing an optical filter that prevents light absorption by melanopsin cells, in which method 800 determines the amount of light D received by the melanopsin cells (eg, formula), as shown in step 802. It may include a step to determine (using (1)). As shown in step 804, the amount of light received over the visual response spectrum can be determined (eg, using equation (2)). As shown in step 806, the figure of merit (FOM) can be determined in relation to the amount of light received by the melanopsin cells and the amount of light received across the visual response spectrum. In other embodiments, the amount of light across the visual response spectrum can be reduced or separated. For example, only one or more parts of the visual response spectrum may be used, or wavelengths outside the visual response spectrum may be considered. The figure of merit can be used to design the optics to reduce and / or prevent photophobic reactions.

[0080] Many embodiments described herein use multilayer dielectric thin films with different refractive indexes. These layers can be applied to many optics (as described herein). By way of example, without any limitation, the embodiments of the optical filter design of the present disclosure have a refractive index of about 1.5 and are added to the posterior surface (ie, the surface closest to the user's eye). Assume a general transparent substrate such as an eyeglass lens with an antireflection coating. Therefore, other substrates with other refractive indices and other substrates with or without an antireflection coating on the back surface are also conceivable. Minor changes in filter design may be required to compensate for the materials of the different substrates and / or the different coatings on those substrates. Further considerations may need to be addressed, such as the affinity of different thin film materials with different substrate materials, which may require further design optimization, and the curvature of the lens substrate. The substrate may include an adhesive layer (eg, a thin layer of chromium) between the substrate or a layer on the substrate and any additional coating.

[0081] There are numerous design techniques for multi-layer long pass filters and notch filters that can be used. For example, software and other design tools are available for designing thin film optical filters. These tools take into account many constraints during optimization, allowing the possibility that either two filter designs will be the same, even if they achieve the same light shielding properties or produce the same physiological results. Can be reduced. Only a few examples appear herein, but are not intended to be limiting at all. Further optimal according to the present disclosure, in order to achieve similar results, in addition to other techniques that may be taken, to provide more ideal properties, or to provide similar properties in a smaller number of layers. Can be implemented.

[0082] In addition, multilayer coatings and other coatings can be applied to colored lenses or substrates. There are multiple reasons why this combination may be desirable. One reason may include that the spectral properties of the coloring can relax the design constraints on the thin film filter. For example, combining FL-41 "basic coloration" with a thin film notch filter can serve to reduce the notch depth required to produce therapeutic results. It may be desirable to consider spectral changes in color transmission in the notch design. This design adjustment can be achieved, for example, by shifting the center wavelength of the notch to compensate for the local slope of the tinted spectral response. Another reason to use basal coloring may be to reduce any unwanted reflection of light entering through the back of the lens. In this case, it may be desirable to use a "flat" or neutral color scheme that does not introduce any of its own color scheme.

[0083] For example, in a filter of one embodiment designed to block light in a certain wavelength range from passing in front of the lens (eg, by reflecting a desired wavelength and moving it away from the user). Light entering the rear side (including light of a blocked wavelength) can be reflected back to the user's eyes. In other words, the light shielded from the front (due to reflection in the case of a multilayer filter) can then be reflected from the rear side. This may not be a concern, primarily if there is a single light source in front of the subject. However, for example, when very bright light is observed, or when there are multiple light sources, this back reflection can be harmful to the user.

[0084] An exemplary technique for producing a long pass filter or notch filter comprises the step of using alternating layers of high index material and low index material. Exemplary low index dielectric materials include MgF ₂ and SiO ₂ . Generally, MgF ₂ is used in a single-layer antireflection film and a multi-layer antireflection film. An exemplary high-refractive index material includes metal oxides such as TiO ₂ , Ti ₃ O ₅ , ZrO ₂ , and Ta ₂ O ₅ , as well as Si ₃ N ₄ . Many other suitable materials can be used, including a polymer layer.

An optical filter that attenuates light near various wavelengths, such as 480 nm, 620 nm, or other specific wavelengths, may follow a similar design. 9 and 10 show the optical filter design of one embodiment and the effect of the filter of this embodiment on the spectrum of light irradiating melanopsin cells that generate effective (and attenuated) action potentials. This design is FL-41 in that 55% of the light absorbed by melanopsin cells is shielded or attenuated.
Aimed to be clinically effective as well as 35 capsules, this design is similar to FL-41 capsules, with only 18% attenuation over the visual response and significantly less visual distortion. It should provide relief of migraine (or photosensitive epilepsy) symptoms. In the present embodiment, the low refractive index material is SiO ₂ , the high refractive index material is TiO ₂ , and MgF ₂ is used as the outermost layer, for a total of 11 layers. The exemplary layers and materials are listed in the following table from the outermost layer (MgF ₂ ) to the innermost layer adjacent to the substrate (TiO _{2 with a} thickness of 165 nm). This filter has FOM≈3.

[0086] The spectral position of the center of the notch filter can be determined by the thickness of each layer of the notch filter. However, while many embodiments herein assume that the spectral position of the notch is about 480 nm, other spectral positions are also conceivable. For example, as more information about the action potential spectrum of the melanopsin transfer pathway is well known, the spectral position can be shifted to, for example, 620 nm according to the new information. Otherwise, in other examples, the spectral positions may be arranged to attenuate wavelengths other than the wavelengths of the action potential spectrum of the melanopsin transfer pathway, for example, to achieve a particular result.

[0087] The width of the notch can be determined by the difference in the refractive index of the different layers. The depth of the notch can be determined by the number of layers. Transmittance outside the notch region can be increased and flattened by including additional layers, and a single-layer or multi-layer anti-reflection coating is applied to the rear surface of the lens to reduce rear reflections. May be included. Further design optimizations may be used to increase the depth of the notch, which can further suppress the excitation of melanopsin cells, but the effect on the visual response spectrum must be considered. Overall suppression can be adjusted on a patient-by-patient basis or by designing one or more common grade filters to help in many cases.

[0088] Greater attenuation of the effective melanopsin action potential spectrum can be achieved by deepening and / or widening the filter notch. 11 and 12, respectively, show embodiments of two exemplary methods using 19 dielectric layers and 15 dielectric layers, respectively. Both result in about 70% attenuation over the melanopsin spectrum, but have slightly different visual response spectral characteristics, so the final choice between the two can be based on the wearer's preference. The 19-layer filter attenuates about 21% of the visual response spectrum, and the 15-layer filter attenuates about 25% of the visual response spectrum. Both filters have a FOM value greater than 2.75, and the 19-layer filter has a FOM value of about 3.3.

[0089] Various designs can achieve significant attenuation over the melanopsin action potential spectrum. 13 and 14 have an FOM value of about 3 and use 19 dielectric layers to shield about 89% of the light, but only about 29% of the visual response spectrum, FL. A notch filter design of one embodiment that provides attenuation of the melanopsin action potential, similar to the -41 55 filter, is shown. The exemplary layers and materials are listed in the following table from the outermost layer (MgF ₂ ) to the innermost layer adjacent to the substrate (TiO _{2 with a} thickness of 160.3 nm).

[0090] Other design considerations may include shielding light emitted at non-vertical angles of incidence. For example, tilting the angle of a thin film filter tends to result in a blueshift in the filter response. This includes, for example, deliberately designing the filter with a slight redshift to minimize or reduce the effect of the angle of incidence, and adding additional layers to increase the width of the filter. It can be adapted either by or in combination.

[0091] FIG. 15 shows a 10-layer filter design in one embodiment, with the center of the notch located at 485 nm with respect to vertically incident light. In vertical incidence, the filter of this embodiment shields about 61% of the amount of light with respect to the melanopsin spectrum and attenuates only about 21% of the light with respect to the visual response spectrum, resulting in a FOM of about 2.9. Brings value.

[0092] FIG. 16 shows the effect of the filter of the embodiment shown in FIG. 15, but the angle of incidence is about 15 degrees. In this embodiment, at this angle of incidence, the occlusion of light to melanopsin is about 61%, with an occlusion of about 20% of the visual response spectrum, resulting in a FOM value of about 3.1.

[0093] The filter of the present embodiment has the layer characteristics described later listed in the following table, from the outermost layer (MgF ₂ ) to the innermost layer (TiO ₂ having a thickness of 127 nm).

[0094] In the filters of the embodiments described in connection with FIGS. 8-15, a low index MgF ₂ layer was used. Other embodiments may not require this material. For example, FIG. 17 shows a filter design of one embodiment that shields about 73% of the melanopsin action potential spectrum (or light intensity) from about 21% of the visible response light intensity and has a FOM value of about 3.5. .. The layer characteristics of the filter design shown in FIG. 17 are listed in the following table from the outermost layer to the innermost layer.

[0095] As mentioned above, it may be desirable to reduce the amount of light reflected into the user's eye from the rear side (ie, the side closest to the user's eye). This can be achieved by the filter design of another embodiment in which the thin film coating can be applied to the colored lens or substrate. In other embodiments, the substrate can be colored by impregnation, coating, other coloring techniques, or a combination thereof. The transmittance of light through the thin film / colored substrate combination can be expressed as the product of the transmittance of the thin film film and the transmittance of the colored substrate.
T (λ) = T _film (λ) T _tint (λ) (4)
It is assumed that the thin film coating is applied only to the front surface of the substrate, and the antireflection coating (T≈1) is applied to the rear surface of the substrate.

[0096] In the case of light entering the rear surface of the substrate, it first passes through the colored portion, is reflected by the thin film filter on the front surface of the substrate, and then passes through the colored portion again before irradiating the user's eyes. In this case, the reflected light can be expressed as the following equation.

[0097] At any particular wavelength, the ratio of transmitted light to reflected light can be set by the transmittance of the thin film coating and the colored portion. For example, if a transmittance of about 20% is desired at the desired wavelength (about 480 nm in this example), only a specific combination of the transmittance of the thin film and the transmittance of the colored portion may be used. Further, if about 10% reflection is desired, only one combination of the transmittance of the thin film and the transmittance of the colored portion is allowed. These relationships can be explained by the following equations.

[0098] The amount of light D received by the melanopsin cells due to the backward reflected light into the user's eye can be expressed in the same manner as the amount of light received by the melanopsin cells due to the transmitted light represented by the formula (1).
DR _-melan = ∫L (λ) R (λ) M (λ) dλ (8)
In the equation, L is the optical spectrum (related to intensity, output, photon / sec, etc.), R is the rearward reflectance of the spectrum, and M is the full width at half maximum of 52 nm, centered at 480 nm from FIG. It is a normalized active potential response spectrum of melanopsin, which is presumed to be the Gaussian function. For generalization, we assume L = 1 so that the description is not limited to any particular light source, but the analysis can be performed on the well-known spectrum of any light source.

[0099] The normalized amount of light received by melanopsin cells due to the backward reflected light can be calculated by the following equation.

[00100] Similar and normalized light quantities can be calculated in relation to the visual response spectrum.
DR _-vis = ∫L (λ) R (λ) V (λ) dλ (10)
In the equation, V represents a normalized visual response spectrum. Ideally, the back reflectance is reduced so that these light intensity values are close to zero.

[00101] The amount of backward reflected light relative to the action potential spectrum of the melanopsin transmission pathway can be determined using equation (8). The amount of backward reflected light with respect to the visual spectrum can be determined using equation (9). The amount of back-reflected light can be used to design and manufacture optical filters. For example, the appropriate level of coloration can be selected based on the maximum desired amount of back-reflected light, whether across the action potential spectrum of the melanopsin transmission pathway, the visual spectrum, or both. Reducing the amount of light received by melanopsin cells and the normalized amount of backward reflected light can reduce the symptoms suffered by photophobic users.

[00102] The table below is an additional implementation using a combination of several possible notch and tinted transmissions, for example, which results in a particular transmission and back reflectance at about 480 nm. The form of the filter design is shown. Note that due to the notch response, the light transmission outside the notch is greater than the light transmission inside the notch, so that the amount of backward reflected light is less than the amount generated at the center of the notch. I want to be. However, although these examples are specific to notches centered around 480 nm, other wavelengths may be selected as described herein.

[00103] Table 5 (Table 1) provides an example in which the transmittance through the front side is different while maintaining a fixed 10% rear side reflectance in a specific wavelength (for example, about 480 nm) or wavelength range. The posterior reflectance of this value is such that light enters the posterior side of the lens and is reflected from the thin film coating on the anterior side into the user's eye by irradiating the lens from the top, bottom, and / or sides. It may be desirable in the case of therapeutic lenses that can be used in "open" spectacle frames where it is permissible. For other types of eyeglass frames (eg, sports glasses, wraparound sunglasses, or other types of frames), other amounts of posterior reflection may be desirable.

[00104] Table 6 provides another embodiment in which a larger posterior reflectance is allowed.
These designs may be more appropriate in the case of "wrap" type spectacle frames or sports frames that prevent light other than the light passing through the front of the lens from entering the eye.

[00105] The filter of another embodiment may include fixing the transmittance of the notch and adjusting the transmittance of the colored portion in order to provide a given rear reflectance value. Examples of these embodiments are shown in Table 3 below.

[00106] The R-value described herein can be used to determine the maximum amount of backward reflected light. For example, an R value of about 0.10 can be used as the desired amount of backward reflected light weighted across the action potential spectrum, the visual spectrum, or both of the melanopsin transmission pathways. Since the R value is based on the desired wavelength to be attenuated, light of other wavelengths can be attenuated based on a filter designed to achieve an R value less than or equal to the value according to the table above. For example, in the case of a wavelength of about 480 nm having an R value of about 0.10, the wavelength is about 470 nm or 49.
The R value at 0 nm can be less than 0.10, for example about 0.09. In general, the R value decreases at wavelengths away from the desired notch center wavelength. For clarity, the tables herein list R-values as decimal values, but these values may also be expressed as percentages.

[00107] These examples are not intended to limit the appropriate combinations for the present disclosure and are provided only to demonstrate some possible combinations that may be appropriate for therapeutic efficacy. .. Any number of other combinations are envisioned, for different levels of photosensitivity of the user, for different diseases, for different uses, and for different types of coloring (eg, gray, FL-41, etc.). Also, it can be suitable for various frame formats.

[00108] Manufacturing considerations may also be considered when performing the filter design. For example, material deposition is typically achieved using sputtering, vapor deposition, or chemical vapor deposition techniques. Sedimentation conditions can be optimized to minimize stress in the thin film material. In many cases, thermal annealing can be performed after deposition to relieve stress in the deposited material, but in many cases annealing is not applicable to plastic lenses. Since spectacle lenses mean a curved substrate, it can be difficult to achieve a certain film thickness during deposition. To achieve a constant film thickness, a change in the positional relationship between the object and the source within the deposition system can be used. For plastic lenses, cold deposition can be used, which can be optimized to produce low stress films.

[00109] The following examples describe the optical filter design tested and the results. The test notch coating was formed on a polycarbonate or CR-39 plano lens with a scratch protection coating. A thin layer of Cr was deposited on the substrate to function as an adhesive layer in the stacking of thin films. The transmission spectrum through an exemplary coated lens is shown in FIG. 18A. The center of the notch is at about 482.9 nm, has a width of about 55.5 nm, and has a minimum transmittance of about 24.5%. The filter of this embodiment shields about 58% of the melanopsin action potential spectrum, shields about 23% over the visible spectrum, and has a FOM value of about 2.6. In contrast, FIG. 18B shows the transmission spectrum of a coated lens using a 620 nm notch filter.

[00110] In a preliminary clinical trial, migraine patients were asked to wear eyeglasses containing the therapeutic notch capsule of FIG. 18A. Participants wore therapeutic lenses for two weeks. In participating in the study, all participants complained of chronic headache, which is defined as having more than 15 days of headache per month. A formal questionnaire, HIT6, was used to assess the effects of headaches on participants' daily lives, both before and after wearing the therapeutic lenses. The table below shows the HIT6 score in tabular form. An average improvement of about 6.6% was seen, along with a significant improvement in the quality of life of the participants.

[00111] In another example, a thin film notch coating was added to the FL-41 tinted lens. The transmission spectrum and the rear reflection spectrum are shown in FIGS. 19 and 20. Various levels of FL-41 coloration were added to a tintable scratch protection layer (also called a hard coating) on polycarbonate or CR-39 lenses. Next, a multilayer notch filter was added to the front side of each lens, and a conventional antireflection film was added to the rear side of each lens. As can be seen from FIGS. 19 and 20, FL-41 coloring significantly reduced posterior reflection. However, in terms of transmittance, the notch response is redshifted due to the slope of FL-41 coloring near 480 nm. This shift can be compensated for, including a slightly blueshifted notch design.

[00112] The following table lists the occlusion levels across the melanopsin spectrum and the visual response spectrum, and the FOM values for each tinting level. Similar results can be expected by using other colorings such as gray coloring such as BPI's "sun gray".

[00113] The coatings described herein can be combined with other techniques. For example, a filter coating can be added to the colored lens, a phototautomerizing material can be incorporated, polarization techniques can be included, other techniques can be combined, or a combination thereof. In addition, a combination of filter techniques can be used, such as adding a nanoparticle filter coating over a multilayer thin film coating. Agents such as electro-optical polymers, liquid crystals, or electro-optical materials including other electro-optical materials, piezoelectric ceramics such as PZT, or piezoelectric materials containing other piezoelectric materials can be used.

[00114] FIG. 21 shows an exemplary embodiment of method 2100 for making an optical filter that reduces the frequency and / or degree of photophobic reaction. Method 2100 can be used to design a filter of at least one embodiment described herein. Method 2100 may include determining a suitable optical spectrum, as shown in step 2102. The steps to determine the proper light spectrum are outdoors, such as indoor fluorescent lighting and / or computer screens in a work, store, or home environment, or sunlight from normal outdoor or sporting activities. It may include studying specific lighting conditions, such as obtaining spectral light intensity measurements in situations such as lighting. As shown in step 2104, the amount of light received by the melanopsin cells can be determined (eg, using formula (1)). As shown in step 2106, the amount of light received over the visual response spectrum can be determined (eg, using equation (2)). As shown in step 2108, an optical filter can be designed and manufactured using the first light intensity and the second light intensity. The first light intensity and the second light intensity can be used to determine the figure of merit (FOM) as described herein. In other embodiments, the amount of light across the visual response spectrum may be considered for one or more parts of the visible spectrum. For example, a larger or smaller range of the visual response spectrum may be used.

[00115] FIG. 22 shows an exemplary embodiment of method 2200 that reduces the frequency and / or degree of photophobic reaction or regulates the circadian cycle. Method 2200 can be used in connection with at least one embodiment of the filter described herein. Method 2200 may include the step of receiving some amount of light, as shown in step 2202. The light received may include direct or indirect light from one or more light sources. As shown in step 2204, less than the first weighted amount of light can be transmitted across the action potential spectrum of the melanopsin cells. As shown in step 2206, a weighted second amount of light can be transmitted across the visual light spectrum. As shown in step 2208, an optical filter can be manufactured using the first light intensity and the second light intensity. The first light intensity and the second light intensity can be used to determine the figure of merit (FOM) as described herein. In other embodiments, the amount of light across the visual response spectrum can be reduced or separated. For example, a larger or smaller range of the visual response spectrum may be used.

[00116] In addition to regulating the exposure of melanopsin ganglion cells to light near 480 nm, the attenuation of light at a wavelength of about 620 nm can also bring about improvements in alleviating the symptoms associated with photosensitivity. Was demonstrated by clinical trials. The wavelength of light at about 620 nm is not thought to act on melanopsin ganglion cells, but the attenuation of light at about 620 nm is light-responsive pain or discomfort, as well as the frequency of migraines and other headaches and Relieving symptoms of photosensitivity in some people, such as / or degree, and may also be effective in treating blepharospasm, post-headache / TBI syndrome, sleep disorders, and epilepsy. Was demonstrated.

[00117] In one embodiment, the improvement can be achieved by attenuating light between about 580 nm and about 650 nm. In other embodiments, the improvement can be achieved by attenuating light between about 600 nm and about 640 nm. In yet another embodiment, the improvement can be achieved by attenuating the light using a filter substantially centered at a wavelength of 620 nm with a full width at half maximum of about 55 nm.

[00118] In addition, the filter can attenuate the wavelength of light in multiple ranges. For example
The filter of one embodiment may attenuate light at about 620 nm in addition to attenuating light at about 480 nm. In another embodiment, the filter may preferentially attenuate wavelengths of light from about 450 nm to about 510 nm and from about 580 nm to about 640 nm. In yet other embodiments, the filter may attenuate light between about 470 and about 490 and between about 610 nm and about 630 nm.

[00119] Optical filters can be manufactured according to the processes described above and using the materials described above. For example, a 620 nm optical filter may include a high pass filter, a low pass filter, or an optical notch filter. The optical notch filter may include multiple layers of dielectric material, nanoparticles dispersed or embedded in the matrix, or a combination thereof. In addition, any of the above combinations may be used in connection with the dye incorporated into the substrate. For example, producing a short pass filter or a notch filter may include the use of alternating layers of high index material and low index material. Exemplary low index dielectric materials include MgF ₂ and SiO ₂ . An exemplary high-refractive index material includes metal oxides such as TiO ₂ , Ti ₃ O ₅ , ZrO ₂ , and Ta ₂ O ₅ , as well as Si ₃ N ₄ . Many other suitable materials can be used, including a polymer layer.

[00120] Similar to the aforementioned embodiment intended to attenuate wavelengths absorbed by melanopsin ganglion cells, optical filters designed to attenuate wavelengths of about 620 nm are manufactured according to a similar FOM. obtain. The amount of light D received at about 620 nm can be expressed as the following equation.
D _{rec, 620} = ∫L (λ) T (λ) R ₆₂₀ (λ) dλ (12)
In the equation, L is the light spectrum (in terms of intensity, output, photons / sec, etc.), T is the spectral transmittance of the filter between the light source and the eye, and R ₆₂₀ is centered on 620 nm. It is an ideal response spectrum at about 620 nm, which can be estimated to be a Gaussian function with a full width at half maximum of 50, 55 or 60 nm, but other values can be assumed to indicate that it is therapeutically effective. For generalization, we assume L = 1 so that the description is not limited to any particular light source, but the analysis can be performed on any light source with a known spectrum.

[00121] Similar amounts of light can be calculated in relation to the visual response spectrum.
D _vis = ∫L (λ) T (λ) V (λ) dλ (13)
In the equation, V represents a normalized visual response spectrum.

[00122] The effect of an optical filter such as a nanoparticle notch filter has been described by taking the ratio of the amount of light calculated using the filter to the amount of light without the filter, for example, as in the following equation. This is to reduce the amount of light.

[00123] The "attenuation" of the amount of light can be expressed, for example, as the following equation.

[00124] FOM comparing light occlusion at about 620 nm with occlusion of visual response spectra
Can also be defined.
This equation represents the ratio of light attenuation to light attenuation over the visible spectrum at about 620 nm, in which it may be desirable that the FOM value> 1. When using the methods described above to estimate the visual response at about 620 nm, the smaller full width at half maximum is used to make the comparison more stringent. For example, when R (λ), which is a Gaussian distribution used for estimation, has a full width at half maximum of 50 nm, a specific optical filter is described as compared with the case where R (λ) having a full width at half maximum of 60 nm is included in the estimation. To do.

[00125] Optical filters may include multilayer waveguides similar to those described for light attenuation sensitive to melanopsin cells, or optical filters may be nanoparticle-based optical filters, color filters. , Coloring, resonant waveguide mode filters, optic filters, or any combination thereof. Nanoparticle-based optical notch filters can include nanoparticles dispersed on or embedded in the surface of the matrix. Thus, such a filter can be used in a substantially transparent base material, such as a lens material for eyeglasses, or can simply be added to its surface. For example, the filter may be placed on the surface of the spectacle lens to attenuate light approaching the user's eye. In other applications, the filter may be placed directly on a light source, such as an electronic display device such as a computer screen, or on a light source such as a light bulb or window.

[00126] Light attenuation by a nanoparticle-based notch filter is determined by the shape of the nanoparticles, the amount or density of nanoparticles on or within the matrix, the composition of the nanoparticles, and the nano. It can be adjusted by the size of the particles and the refractive index of the base material. Therefore, the attenuation spectrum of the nanoparticle-based optical notch filter has the desired wavelength at the center of the curve and the maximum attenuation at the desired wavelength value, producing an attenuation curve with the appropriate shape and full width at half maximum. It can be adjusted to a specific curve by selecting the material and distribution that bring about the thing.

[00127] For example, increasing the index of refraction of the base material of nanoparticles is similar to using longer particle dimensions and / or other metals, including solid particles and core-shell particles. The attenuation spectrum can be shifted towards longer wavelengths. Since the attenuation is due, at least in part, to localized surface plasmon resonance (LSPR), the attenuation spectrum changes. Scattering due to LSPR is proportional to the relative index of refraction of the base metal. Therefore, as the refractive index of the base material increases, not only the attenuation spectrum shifts to red, but also the amount of scattering and, as a result, the amount of light attenuation increase.

[00128] The location and amount of scattering due to LSPR depends, at least in part, on the relative index of refraction between the particles and the base metal. Therefore, the relative index of refraction can also be changed by changing the composition of the nanoparticles. The nanoparticles can be a solid consisting of a single material or a core-shell configuration comprising a core of the first material and a shell of the second material. In either case, the material can be a single element, compound, or alloy. As mentioned above, the nanoparticles are metal nanoparticles (eg, Al, Ag, Au, Cu, Ni, Pt), dielectric nanoparticles (eg, TiO ₂ , Ta ₂ O _5, etc.), semiconductor nanoparticles or quantum dots. It may include (eg, Si, GaAs, GaN, CdSe, CdS, etc.), magnetic nanoparticles, core-shell nanoparticles consisting of one material in the core and another material acting as a shell, other nanoparticles, or a combination thereof. For example, increasing the ratio of Ag in Ag / Al alloy solid nanoparticles can increase the amplitude of the attenuation curve with respect to the nanoparticles and can also cause a redshift.

[00129] In addition, the nanoparticles used can have a cross section that includes circles, ellipses, rectangles, hexagons, octagons, or other polygons. Spherical particles have the clearest spectrum because they have a single narrow main peak that allows optimization using resizing and compositional changes. However, it is possible to use a combination of particles of other shapes to form the desired filter spectrum. For example, the extinction spectrum of a 40 nm spherical nanoparticles filter can be broadened simply by introducing cubic or octahedral nanoparticles of equivalent size.

[00130] In contrast, the decay curve of core-shell nanoparticles can be adjusted by changing the relative thickness of the core and shell. For example, reducing the thickness of the Ag shell relative to the dimensions of the SiO ₂ core can reduce the full width at half maximum of the attenuation spectrum. The shape of these particles can be spherical, ellipsoidal, another shape, or a combination thereof. The shape of the particles can also affect the shape and amplitude of the decay curve. In one embodiment, the optical filter comprises spherical core-shell nanoparticles. In another embodiment, the spherical core-shell nanoparticles include an Ag shell and a Si core. In yet another embodiment, the spherical Ag / Si core shell nanoparticles include an Ag shell with a radial thickness of 45 nm and a Si core with a radius of 15 nm.

[00131] FIG. 23 shows a nanoparticle-based optical filter used in connection with a multilayer thin film filter forming the composite filter 2300. The first filter may attenuate light in the first wavelength range, thereby substantially reducing or eliminating those wavelengths in the light spectrum entering the second filter. In the illustrated embodiment, the ambient light 2302 can enter a filter containing nanoparticles 2304 that can be placed on a base material 2306 placed on the surface of the thin film filter 2308 or embedded in the base material 2306. Alternatively, or in addition, the thin film filter and the nanoparticle-based filter can be placed on both sides of the substrate, such as an spectacle lens. In another embodiment, the nanoparticles can be embedded within a thin film filter and one or more layers of the thin film can be the base material for a nanoparticle-based filter. The ambient light 2302 entering the base material 2306 in which the nanoparticles 2304 are embedded can be sunlight. The attenuated light 2310 entering the thin film filter 2308 may include a reduced amount of light in the range attenuated by the nanoparticles 2304. The filtered light 2312 exiting the composite filter 2300 can be attenuated in two wavelength ranges. Similarly, a "two notch" filter can be implemented entirely by the use of a multilayer thin film coating.

[00132] FIG. 24 shows an embodiment of Method 2400 for manufacturing a composite optical filter that reduces the frequency and / or degree of photophobic reaction. Method 2400 can be used to design a composite filter of at least one embodiment described herein. Method 2400 may include determining a suitable optical spectrum, as shown in step 2402. The steps to determine the appropriate light spectrum are outdoors, such as indoor fluorescent lighting and / or computer screens in a work, store, or home environment, or sunlight from normal outdoor or sporting activities. In situations such as lighting, it may involve studying specific lighting conditions, such as obtaining spectral light intensity measurements.

[00133] As shown in step 2404, the first amount of light received by the subject can be determined (eg, using equation (1)). As shown in step 2406, the second amount of light received by the human eye at a wavelength of about 620 nm can be estimated (eg, using equation (12)). As shown in step 2408, the amount of third light received over the visual response spectrum can be determined (eg, using equation (13)). As shown in step 2410, an optical filter can be designed and manufactured using a first light quantity, a second light quantity, and a third light quantity. As described herein, each of the first and second light quantities can be used with a third light quantity to determine the respective figure of merit (FOM). In other embodiments, the amount of light over the visual response spectrum may be considered for one or more portions of the visible spectrum. For example, a larger or smaller range of the visual response spectrum may be used.

[00134] FIG. 25 shows an embodiment of Method 2500 using a composite filter that reduces the frequency and / or degree of photophobic reaction or regulates the circadian cycle. Method 2500 can be used in connection with the composite filter of at least one embodiment described herein. Method 2500 may include the step of receiving some amount of light, as shown in step 2502. The light received may include direct or indirect light from one or more light sources. As shown in step 2504, a first amount of preferentially attenuated light can be transmitted across the action potential spectrum of the melanopsin cells. As shown in step 2506, a second amount of preferentially attenuated light can be transmitted in the wavelength range at about 620 nm. As shown in step 2508, a third amount of light is then transmitted to the human eye. In other embodiments, the amount of light across the visual response spectrum may be reduced or separated. For example, a larger or smaller range of the visual response spectrum may be used.

[00135] Efficacy tests have been performed to demonstrate the benefits of attenuating light near about 480 nm and 620 nm. Preliminary trials included a predicted double-mask cross-clinical trial to determine the effectiveness of a customized thin-film spectacle capsule in the treatment of chronic migraine. The subject wore two different glasses during the test. One coating is a notch filter at 480 nm. The other coating was a notch filter at 620 nm. Typical transmission spectra of gray colored lenses with various coatings used in this test are shown in FIGS. 23A and 23B. The 480 nm notch filter shown blocks about 68% of the light absorption by melanopsin and 42% of the visible light. The 620 nm notch filter shown blocks about 66% of light absorption centered on 620 nm with a width of about 55 nm and about 42% of visible light. The 480 nm filter used in the test provides an average of 68 ± 6% occlusion and an average of 44 ± 4% occlusion at about 480 nm. The 620 nm filter used in the test provides an average of 67 ± 2% occlusion and an average of 43 ± 4% occlusion at about 620 nm. Neither the subject nor the clinical coordinator was informed of which lenses contained a 480 nm notch filter and which contained a 620 nm notch filter. The subject in the study must be diagnosed with chronic migraine headaches, which means that the subject has at least 15 days of headache per month. People who have at least 15 days of headache per month are considered to be the most severely symptomatic migraine patients.

[00136] To assess the effectiveness of the intervention, a six-question "headache impact test"("HIT (Headache Impact Test) -6") was selected as the primary endpoint metric. HIT-6 is a six-question tool designed and validated to assess the effects of headaches on human life. Scores are continuous variables ranging from a minimum of 36 to a maximum of 78. A score of less than 50 indicates that the headache has little effect on a person's life, a score of 50-55 represents a "some effect", and a score of 56-59 represents a "significant effect". A score above 60 corresponds to the "very serious effect" of a headache.

[00137] The subject first performed "pre-purification" for 4 weeks without wearing the test lens. This period helped determine the baseline characteristics of the subject's headache. The subject was first randomly determined which lens to wear using block randomization. The subject was instructed to wear eyeglasses throughout the day for two weeks. The subject then experienced a two-week "cleansing" period in which the test lens was not worn. The subject then wore another lens for another two weeks. Finally, the subject experienced a final "post-cleaning" period in which the test lens was not worn, which determined the "final point" of the exit for headache characteristics.

[00138] There is considerable variability in the frequency and severity of headaches. In some cases, this variability can occur in the same patient. Due to variability, a "pre-purification" period and a "post-cleaning" period have been added. These additional periods when the test lens was not worn minimized the effect of "reference variation" on the test subject.

[00139] As a result of conducting the HIT-6 questionnaire before the test and after each period of the test, 6 questionnaires were conducted for each subject. Forty-eight participants first participated in the test, and 37 participants completed a series of tests. The standard HIT-6 score of the 37 subjects who completed the test was 64.5. Thirty-three (89%) of the 37 patients received a standard HIT-6 score of 60 or higher. According to HIT-6's interpretation, these 33 patients suffer from headaches that have a "very serious impact" on their lives. Both 480 nm and 620 nm filter lenses statistically showed a significant reduction in HIT-6 values.

[00140] Of the 37 participants who completed the test, 9 subjects were able to leave the HIT-6 category of "very serious effects" while wearing a 480 nm lens. Yes, 5 subjects can wear a 620nm lens and get out of this category, and 5 people can get out of this category by wearing any of these lenses. did it. Ten subjects experienced at least 6 points of improvement in HIT-6 when wearing a 480 nm lens, and 10 subjects experienced at least 6 points in HIT-6 when wearing a 620 nm lens. Three subjects experienced at least 6 points of improvement in HIT-6 when wearing any of these lenses. This analysis shows that wearing either a 480 nm or 620 nm spectacle lens resulted in a statistically significant reduction in HIT-6. However, when the effect of the 480 nm lens was compared with that of the 620 nm lens, there was no substantial difference (p = 0.195).

[00141] Percentage of days with severe headaches, percentage of days when activity needed to be changed or the subject needed to sleep, and percentage of days when the subject needed dementia. Secondary endpoints collected from the diary, including, behaved similarly to the primary endpoint for either 480 nm or 620 nm spectacle lenses. That is, the subject wore either a 480 nm or 620 nm lens and experienced a significant reduction in these parameters. In all of these three evaluation items, when the effect of the 480 nm lens was compared with that of the 620 nm lens, there was no substantial difference.

[00142] Melanopsin Melanopsin in ganglion cells is a bistable pigment. Melanopsin can be isomerized during exposure to light of a particular wavelength. FIG. 27 is a graph 2700 schematically showing the cyclic isomerization of bistable dyes when the dyes are exposed to light of different wavelengths. The bistable dye may include a first isoform showing a first absorption spectrum of 2702. The first absorption spectrum absorbs the first wavelength 2704. The first isoform of the bistable dye can react with the first wavelength 2704. The first wavelength 2704 can isomerize the bistable dye and induce a light signaling cascade in the associated cell or membrane. In one embodiment, the bistable dye can be melanopsin, and exposure to the first wavelength 2704 can induce a light signaling cascade in melanopsin ganglion cells. Exposure to the first wavelength can isomerize the bistable dye from the first isoform to the second isoform. The first isoform can be the active 11-cis isoform of melanopsin. The second isoform can be an inert metamelanopsin isoform. Isomerization of the active 11-cis isoform can result in an optical signaling cascade.

[00143] The second isoform may exhibit a second absorption spectrum of 2706. The second absorption spectrum 2706 can absorb the second wavelength 2708. The second isoform of the bistable dye can react with the second wavelength 2708. In one embodiment, the first isoform can be the active isoform of the bistable dye and the second isoform can be the inactive isoform of the bistable dye. In other embodiments, the first isoform may be the bistable dye inactive isoform and the second isoform may be the bistable dye active isoform. In yet another embodiment, the first isoform may be the active isoform of melanopsin and the second isoform may be the inactive isoform of melanopsin.

[00144] FIG. 28 shows a graph 2800 of the active absorption spectrum 2802 and the inactive absorption spectrum 2804 of melanopsin. The active absorption spectrum 2802 and the inactive absorption spectrum 2804 correspond to the active isoform of melanopsin and the inactive isoform of melanopsin, respectively. The terms "active" and "inactive" refer to the bioactivity of a dye and must be understood as the ability of the dye to contribute to the human photophobic response rather than the ability of the dye to absorb light. The active absorption spectrum 2802 can take a maximum value at about 484 nm. The Inactive Absorption Spectrum 2804 can take a maximum value at about 587 nm.

The Inactive Isoform of Melanopsin can absorb wavelengths of light according to the Inactive Absorption Spectrum 2804. The light absorbed by the Inactive Isoform of Melanopsin can contribute to the conversion of the Inactive Isoform to the active form of Melanopsin. The active form of melanopsin can contribute to the human photophobic response. In at least one embodiment, the attenuation of light absorbed by the inert isoform interferes with the isomerization of melanopsin, light-responsive pain or discomfort, and the frequency and / or frequency of migraines with other headaches. It can alleviate the symptoms of photosensitivity in some people, such as degree, and can also be effective in some people in the treatment of blepharospasm, post-concussion / TBI syndrome, sleep disorders, epilepsy.

[00146] In addition to regulating the exposure of melanopsin ganglion cells to light near 480 nm and / or 620 nm, the attenuation of light at the maximum absorption of the inactive absorption spectrum in the case of the inactive isoform of melanopsin Improvements can also be achieved in reducing the symptoms associated with photosensitivity. For example, an optical filter centered on a wavelength of about 590 nm can attenuate the light absorbed by the Inactive Isoform of melanopsin.

[00147] In one embodiment, improvements can be achieved by attenuating light between about 560 nm and about 620 nm. In another embodiment, the improvement can be achieved by attenuating the light between about 570 nm and about 610 nm. In yet another embodiment, the improvement can be achieved by attenuating the light using a filter substantially centered at a wavelength of 590 nm with a full width at half maximum of about 50 nm.

[00148] In addition, the filter can attenuate the wavelength of light in multiple ranges. For example
The filter of one embodiment may attenuate the light absorbed by the Inactive Isoform of Melanopsin and the light absorbed by the Active Isoform of Melanopsin. In one embodiment, the filter may attenuate light at about 590 nm in addition to attenuating light at about 480 nm. In another embodiment, the filter may preferentially attenuate wavelengths of light from about 450 nm to about 510 nm and from about 560 nm to about 620 nm. In yet another embodiment, the filter may attenuate light between about 470 and about 490 and between about 580 nm and about 600 nm.

[00149] Similar to the 480 nm filter and the 620 nm filter described above, an optical filter capable of attenuating 590 nm light may include a high pass filter, a low pass filter, an optical notch filter, or a combination thereof. The optical notch filter may include multiple layers of dielectric material, nanoparticles dispersed or embedded in the matrix, or a combination thereof. In addition, any of the above combinations may be used in connection with the dye incorporated into the substrate. For example, producing a short pass filter or a notch filter may include the use of alternating layers of high index material and low index material. Exemplary low index dielectric materials include MgF ₂ and SiO ₂ . An exemplary high-refractive index material includes metal oxides such as TiO ₂ , Ti ₃ O ₅ , ZrO ₂ , and Ta ₂ O ₅ , as well as Si ₃ N ₄ . Many other suitable materials can be used, including a polymer layer.

[00150] Similar to the embodiments described above in which the wavelength absorbed by the active isoform of melanopsin is intended to be attenuated, the optical filter designed to attenuate the wavelength of about 590 nm follows a similar FOM. Can be manufactured. The amount of light D received at about 590 nm can be expressed as the following equation.
D _{rec, 590} = ∫L (λ) T (λ) R ₅₉₀ (λ) dλ (15)
In the equation, L is the light spectrum (in terms of intensity, output, photons / sec, etc.), T is the spectral transmittance of the filter between the light source and the eye, and R ₅₉₀ is centered around ₅₉₀ nm. , An ideal response spectrum at about 590 nm, which can be estimated to be a Gaussian function with a full width at half maximum of 50, 55, or 60 nm, but other values can be assumed to indicate that it is therapeutically effective. For generalization, we assume L = 1 so that the description is not limited to any particular light source, but the analysis can be performed on any light source with a known spectrum.

[00151] Similar amounts of light can be calculated in relation to the visual response spectrum.
D _vis = ∫L (λ) T (λ) V (λ) dλ (16)
In the equation, V represents a normalized visual response spectrum.

[00152] The effect of an optical filter such as a nanoparticle notch filter is explained by taking the ratio of the amount of light calculated using the filter to the amount of light without the filter, for example, as in the following equation. As such, it is to reduce the amount of light.

[00153] The "attenuation" of the amount of light can be expressed, for example, by the following equation.

[00154] FOM comparing light occlusion at about 590 nm with occlusion of visual response spectra
Can also be defined as:
This equation represents the ratio of light attenuation to light attenuation over the visible spectrum at about 590 nm, in which it may be desirable that the FOM value> 1. Using the aforementioned method of estimating the visual response at about 590 nm, the smaller the full width at half maximum is used, the more rigorous the comparison becomes. For example, when R (λ), which is the Gaussian distribution used for estimation, has a full width at half maximum of 50 nm, a more specific optical filter is used as compared with the case where R (λ) having a full width at half maximum of 60 nm is included in the estimation. explain.

[00155] FIG. 29 shows a method 2900 for alleviating the symptoms associated with the photophobic reaction. Method 29
00 includes a step 2902 to receive light, a step 2904 to attenuate the first wavelength, and optionally a step 2906 to attenuate the second wavelength. Subsequently, the attenuation of the first wavelength can interfere with the bistable dye circulation described with reference to FIG. 27 (step 2908). In one embodiment, the first wavelength can be determined by the maximum value of the active or inert absorption spectrum of the bistable dye. In another embodiment, the first wavelength can be determined by the maximum value of the active absorption spectrum 2802 of melanopsin, as described with reference to FIG. 28, or the maximum value of the inactive absorption spectrum 2804. In yet another embodiment, the first wavelength can be 480 nm. In another embodiment, the first wavelength can be 590 nm.

[00156] Attenuating a wavelength should be understood to mean preferentially attenuating that wavelength or the range containing that wavelength compared to other parts of the visible spectrum. For example, attenuating a wavelength of 590 nm may include transmitting less light at a wavelength of 590 nm or about 590 nm than other light in the visible spectrum. In another example, attenuating a wavelength of 590 nm may include shielding substantially all of the light at a wavelength of 590 nm or about 590 nm and transmitting other light in the visible spectrum.

[00157] Attenuating the second wavelength 2906 may include attenuating a portion of the second wavelength that is different from the first wavelength being attenuated. In one embodiment, the second wavelength can be determined by the maximum value of the active or inert absorption spectrum of the bistable dye. In another embodiment, the first wavelength can be determined by the maximum value of the melanopsin active absorption spectrum 2802 or the maximum value of the melanopsin inactive absorption spectrum 2804 described in connection with FIG. 28. In yet another embodiment, the first wavelength can be 480 nm. In another embodiment, the first wavelength can be 590 nm.

[00158] Attenuating the first wavelength 2904 and optionally the second wavelength 2906
Attenuating can interfere with bistable dye circulation. Attenuating the first wavelength 2904 can suppress the isomerization of the bistable dye from the first isoform to the second isoform. The first isoform can be an active or inactive isoform. Attenuating the second wavelength 2906 can suppress the isomerization of the bistable dye returning from the second isoform to the first isoform.

An optical filter capable of attenuating light at a wavelength of 590 nm or about 590 nm is any of the above, such that a low pass filter, a high pass filter, or an optical notch filter preferentially attenuates light at 590 nm. It can be manufactured and / or adjusted by the process. Filters can include multilayer dielectrics, nanoparticle embedding coatings, color filters, coloring, resonant waveguide mode filters, rugate filters, and any combination thereof. Filters further include nanoparticles embedded coatings such as metal nanoparticles, dielectric nanoparticles, semiconductor nanoparticles, quantum dots, magnetic nanoparticles, or core-shell particles with a core material in the core and a shell material that acts as a shell. Can include.

[00160] As used herein, "approximate" and "abou".
The terms "t)", "near", and "substantially" still represent quantities close to the stated amount that perform the desired function or achieve the desired result. For example, the terms "approximate", "about", and "substantially" are less than 10%, less than 5%, less than 1%, less than 0.1% of the amount described. , And amounts in the range less than 0.01%.

[00161] Although the present invention is described in the context of the above embodiments, these descriptions are not intended to limit the scope of the invention to the particular embodiments described, but rather these descriptions. It should be noted that it is intended to cover alternatives, variants, and equivalents that may be included within the scope of the present invention. Any component of the above embodiment may be combined with any other component of any of the above embodiments. For example, any of the manufacturing methods or light attenuation methods described above can be combined with the optical filters described and the associated wavelengths. As such, the scope of the invention fully embraces other embodiments that may be apparent to those skilled in the art, and the scope of the invention is limited only by the appended claims.

[00161] Although the present invention is described in the context of the above embodiments, these descriptions are not intended to limit the scope of the invention to the particular embodiments described, but rather these descriptions. It should be noted that it is intended to cover alternatives, variants, and equivalents that may be included within the scope of the present invention. Any component of the above embodiment may be combined with any other component of any of the above embodiments. For example, any of the manufacturing methods or light attenuation methods described above can be combined with the optical filters described and the associated wavelengths. As such, the scope of the invention fully embraces other embodiments that may be apparent to those skilled in the art, and the scope of the invention is limited only by the appended claims.
[Form 1]
A device that reduces the frequency and / or degree of photophobic reaction by controlling the exposure of cells to light containing a wavelength of about 590 nm, or regulates the circadian cycle.
An optical filter configured to transmit light below the first light intensity at a wavelength of about 590 nm and to transmit light above the weighted second light intensity over the visual spectral response.
A device equipped with.
[Form 2]
The first amount of light is substantially the entire amount of light at the wavelength of about 590 nm.
The second amount of light is approximately the entire amount of light outside the wavelength of about 590 nm, weighted over the visual response spectrum.
The device according to the first embodiment.
[Form 3]
The first amount of light is substantially all of the light above the short pass filter wavelength between about 560 nm and 620 nm.
The second amount of light is all light over the visual spectral response, including wavelengths below the short pass filter wavelength.
The device according to the first embodiment.
[Form 4]
The second light intensity includes a third light intensity including a wavelength of less than about 590 nm or more than the wavelength of about 590 nm.
The device according to the first embodiment.
[Form 5]
The second light amount includes a third light amount including a wavelength of less than about 590 nm and a fourth light amount including a wavelength of more than about 590 nm.
The device according to the first embodiment.
[Form 6]
The first amount of light is the amount of light ( _{Drec, 590} ) received by the receptor cell of the subject at the wavelength of about 590 nm.
The second amount of light is the amount of light (D _vis ) received over the visual response spectrum.
The ratio including the first light amount and the second light amount is defined as a figure of merit (FOM).
The figure of merit is
Determined by
In the formula, D _{rec, 590} (T = 1) is the first amount of light when there is no optical filter, and D _vis (T = 1) is the second amount of light when there is no optical filter. ,
The device according to the first embodiment.
[Form 7]
The figure of merit of the optical filter is about 1, greater than about 1, greater than about 1.3, greater than about 1.5, greater than about 1.8, greater than about 2.75, greater than about 3. Larger or greater than about 3.3,
The device according to the sixth embodiment.
[Form 8]
The optical filter includes a multilayer dielectric, a nanoparticle embedded coating, a color filter, a coloring, a resonant waveguide mode filter, a lugate filter, and any combination thereof.
The device according to the first embodiment.
[Form 9]
The nanoparticles-embedded coating comprises at least one of metal nanoparticles, dielectric nanoparticles, semiconductor nanoparticles, quantum dots, magnetic nanoparticles, or core-shell particles having a core material in the core and a shell material acting as a shell. ,
The device according to the eighth embodiment.
[Form 10]
The at least metal nanoparticles contain at least one of Al, Ag, Au, Cu, Ni, Pt, or other metal nanoparticles.
The dielectric nanoparticles contain at least one of TiO ₂ , Ta ₂ O ₅ , or other dielectric nanoparticles.
The device according to embodiment 9.
[Form 11]
The semiconductor nanoparticles or quantum dots contain at least one of Si, GaAs, GaN, CdSe, CdS, or other semiconductor nanoparticles.
The device according to embodiment 9.
[Form 12]
The shape of the embedded nanoparticles in the nanoparticles embedded coating is spherical, elliptical, or another shape.
The device according to embodiment 9.
[Form 13]
A method of reducing the frequency and / or degree of photophobic reaction using light with a wavelength of about 590 nm and the visual spectral response of the human eye, or adjusting the circadian cycle.
Steps that receive some amount of light,
A step of transmitting light less than the first amount of light at the wavelength of about 590 nm using the apparatus according to the first embodiment.
A step of transmitting a weighted second amount of light over the visual spectrum response using the apparatus according to embodiment 1.
How to include.
[Form 14]
By controlling the exposure of cells in the human eye to light using light at a wavelength of about 590 nm and the visual spectral response of the human eye, the frequency and / or degree of photophobic response is reduced or approximated. A system that regulates the daily cycle
With the base material
A first layer arranged on the base material, the first layer containing a high refractive index material, and
A second layer, which is arranged adjacent to the first layer and contains a low refractive index material, and a second layer.
System with.
[Form 15]
The high refractive index material of the first layer is TiO ₂ .
The low refractive index material of the second layer is SiO ₂ .
Further comprising one or more additional alternating adjacent layers of TiO ₂ and SiO ₂ .
The first additional layer is adjacent to the second layer
The last additional layer can be MgF ₂ , SiO ₂ or TiO ₂ and is adjacent to the outer layer,
The system according to embodiment 14.
[Form 16]
A device that reduces the frequency and / or degree of photophobic reaction or regulates the circadian cycle by controlling the exposure of the human eye to light containing wavelengths of about 590 nm and about 480 nm.
It is configured to transmit light less than the first weighted amount of light over the wavelength range of about 590 nm and about 480 nm, and to transmit light more than the second weighted amount of light over the visual spectral response. Composite optical filter,
A device equipped with.
[Form 17]
The optical filter comprises at least one of a multilayer dielectric coating, a nanoparticle embedded coating, a color filter, a coloring, a resonant waveguide mode filter, a lugate filter, or any combination thereof.
The device according to embodiment 16.
[Form 18]
The nanoparticles-embedded coating comprises at least one of metal nanoparticles, dielectric nanoparticles, semiconductor nanoparticles, quantum dots, magnetic nanoparticles, or core-shell particles having a core material in the core and a shell material acting as a shell. ,
The device according to embodiment 16.
[Form 19]
At least the metal nanoparticles contain at least one of Al, Ag, Au, Cu, Ni, Pt, or other metal nanoparticles.
The dielectric nanoparticles contain at least one of TiO ₂ , Ta ₂ O ₅ , or other dielectric nanoparticles.
The device according to embodiment 18.
[Form 20]
A method of using the action potential spectrum of melanopsin cells of the human eye and the visual spectral response of the human eye to reduce the frequency and / or degree of photophobic response or to regulate the circadian cycle.
Steps that receive some amount of light,
A step of preferentially attenuating light over the absorption spectrum of the melanopsin isoform using the apparatus of embodiment 16.
How to include.

Claims (20)

A device that reduces the frequency and / or degree of photophobic reaction by controlling the exposure of cells to light containing a wavelength of about 590 nm, or regulates the circadian cycle.
An optical filter configured to transmit light below the first light intensity at a wavelength of about 590 nm and to transmit light above the weighted second light intensity over the visual spectral response.
A device equipped with. The first amount of light is substantially the entire amount of light at the wavelength of about 590 nm.
The second amount of light is approximately the entire amount of light outside the wavelength of about 590 nm, weighted over the visual response spectrum.
The device according to claim 1. The first amount of light is substantially all of the light above the short pass filter wavelength between about 560 nm and 620 nm.
The second amount of light is all light over the visual spectral response, including wavelengths below the short pass filter wavelength.
The device according to claim 1. The second light intensity includes a third light intensity including a wavelength of less than about 590 nm or more than the wavelength of about 590 nm.
The device according to claim 1. The second light amount includes a third light amount including a wavelength of less than about 590 nm and a fourth light amount including a wavelength of more than about 590 nm.
The device according to claim 1. The first amount of light is the amount of light ( _{Drec, 590} ) received by the receptor cell of the subject at the wavelength of about 590 nm.
The second amount of light is the amount of light (D _vis ) received over the visual response spectrum.
The ratio including the first light amount and the second light amount is defined as a figure of merit (FOM).
The figure of merit is
Determined by
In the formula, D _{rec, 590} (T = 1) is the first amount of light when there is no optical filter, and D _vis (T = 1) is the second amount of light when there is no optical filter. ,
The device according to claim 1. The figure of merit of the optical filter is about 1, greater than about 1, greater than about 1.3, greater than about 1.5, greater than about 1.8, greater than about 2.75, greater than about 3. Larger or greater than about 3.3,
The device according to claim 6. The optical filter includes a multilayer dielectric, a nanoparticle embedded coating, a color filter, a coloring, a resonant waveguide mode filter, a lugate filter, and any combination thereof.
The device according to claim 1. The nanoparticles-embedded coating comprises at least one of metal nanoparticles, dielectric nanoparticles, semiconductor nanoparticles, quantum dots, magnetic nanoparticles, or core-shell particles having a core material in the core and a shell material acting as a shell. ,
The device according to claim 8. The at least metal nanoparticles contain at least one of Al, Ag, Au, Cu, Ni, Pt, or other metal nanoparticles.
The dielectric nanoparticles contain at least one of TiO ₂ , Ta ₂ O ₅ , or other dielectric nanoparticles.
The device according to claim 9. The semiconductor nanoparticles or quantum dots contain at least one of Si, GaAs, GaN, CdSe, CdS, or other semiconductor nanoparticles.
The device according to claim 9. The shape of the embedded nanoparticles in the nanoparticles embedded coating is spherical, elliptical, or another shape.
The device according to claim 9. A method of reducing the frequency and / or degree of photophobic reaction using light with a wavelength of about 590 nm and the visual spectral response of the human eye, or adjusting the circadian cycle.
Steps that receive some amount of light,
A step of transmitting light less than the first amount of light at the wavelength of about 590 nm using the apparatus according to claim 1.
A step of transmitting a weighted second amount of light over the visual spectral response using the apparatus of claim 1.
How to include. By controlling the exposure of cells in the human eye to light using light at a wavelength of about 590 nm and the visual spectral response of the human eye, the frequency and / or degree of photophobic response is reduced or approximated. A system that regulates the daily cycle
With the base material
A first layer arranged on the base material, the first layer containing a high refractive index material, and
A second layer, which is arranged adjacent to the first layer and contains a low refractive index material, and a second layer.
System with. The high refractive index material of the first layer is TiO ₂ .
The low refractive index material of the second layer is SiO ₂ .
Further comprising one or more additional alternating adjacent layers of TiO ₂ and SiO ₂ .
The first additional layer is adjacent to the second layer
The last additional layer can be MgF ₂ , SiO ₂ or TiO ₂ and is adjacent to the outer layer,
The system according to claim 14. A device that reduces the frequency and / or degree of photophobic reaction or regulates the circadian cycle by controlling the exposure of the human eye to light containing wavelengths of about 590 nm and about 480 nm.
It is configured to transmit light less than the first weighted amount of light over the wavelength range of about 590 nm and about 480 nm, and to transmit light more than the second weighted amount of light over the visual spectral response. Composite optical filter,
A device equipped with. The optical filter comprises at least one of a multilayer dielectric coating, a nanoparticle embedded coating, a color filter, a coloring, a resonant waveguide mode filter, a lugate filter, or any combination thereof.
The device according to claim 16. The nanoparticles-embedded coating comprises at least one of metal nanoparticles, dielectric nanoparticles, semiconductor nanoparticles, quantum dots, magnetic nanoparticles, or core-shell particles having a core material in the core and a shell material acting as a shell. ,
The device according to claim 16. At least the metal nanoparticles contain at least one of Al, Ag, Au, Cu, Ni, Pt, or other metal nanoparticles.
The dielectric nanoparticles contain at least one of TiO ₂ , Ta ₂ O ₅ , or other dielectric nanoparticles.
The device according to claim 18. A method of using the action potential spectrum of melanopsin cells of the human eye and the visual spectral response of the human eye to reduce the frequency and / or degree of photophobic response or to regulate the circadian cycle.
Steps that receive some amount of light,
A step of preferentially attenuating light over the absorption spectrum of an isoform of melanopsin using the apparatus of claim 16.
How to include.